Paxillin interacts with bcl‐2 through its LD4 domain

Abstract

Paxillin is an adapter protein implicated in growth factor and integrin mediated signal transduction pathways. It is the founding member of a family of proteins that include Hic-5 and leupaxin, which share many of paxillin’s structural characteristics. Paxillin can function during the regulation of cell migration and spreading. Loss of paxillin results in inhibition of focal adhesion turnover, loss of polarization and loss of directional motility. However, its role during organogenesis requires further delineation. Paxillin-deficient mice are abnormal by embryonic day 9.5, suggesting that paxillin may play an important role during development. Previous work from this laboratory demonstrated that paxillin interacted with bcl-2’s BH4 domain influencing branching morphogenesis in the embryonic kidney. Here studies were performed to determine the bcl-2 binding motif in paxillin. Bcl-2 was found to associate with the amino-terminal portion of paxillin, specifically the LD4 motif. This interaction was found to be specific for paxillin since Hic-5 and leupaxin LD4 motifs did not associate with bcl-2. Furthermore, incubation of embryonic kidneys with the LD4 domain had a profound effect on ureteric bud branching and morphogenesis. These data suggest that bcl-2 association with paxillin plays a unique role during kidney development that paxillin’s other family members may not be able to fulfill.